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SEPSIS - MENINGITIS - MALARIA Pr. B. Vandercam Consultation Maladies Infectieuses et Tropicales Cliniques Universitaires St-Luc Octobre 2004.

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Présentation au sujet: "SEPSIS - MENINGITIS - MALARIA Pr. B. Vandercam Consultation Maladies Infectieuses et Tropicales Cliniques Universitaires St-Luc Octobre 2004."— Transcription de la présentation:

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2 SEPSIS - MENINGITIS - MALARIA Pr. B. Vandercam Consultation Maladies Infectieuses et Tropicales Cliniques Universitaires St-Luc Octobre 2004

3 Sepsis Focus Absence of focus –Purpura fulminans –Community acquired sepsis immunocompentent adult –Nosocomial sepsis immunocompetent adult –IV DU –Asplenic (anatomic or functional) –Neutropenia –Toxic shock syndrome

4 Working definitions associated with sepsis and related disorders

5 Source of infection Anamnesis (pets, travel, household, …) Physical examination (purpura, scar …) Blood culture Urine culture RX thorax Echo (scan abdo) obstacle abscess collection Echo cardio

6 Activated protein C (- 6 %) Corticosteroids (low (HC mg/day) - long (5-7d) ) Intensive insuline therapy (- 17%) Volume resuscitation (- 15%)

7 Prior medicare database analyses MEEHAN T. Jama 1997; 278:2080 Mortality increased significantly with delay in first Abx dose > 8 hrs (registration to dose) GLEASON PP. Arch Intern Med 1999, 159:2562 Mortality based on abx (OR) Cephalosporin 1.0 Cephalosporin + mac 0.76 Fluoroquinolone0.64

8 Method : review of Medicare database for patients > 65 yrs hospitalized with x-ray confirmed CAP Period reviewed : July ’98 - March ’99 Patients : PSI score : III - 47 % IV - 24 %

9 Results

10 Skin lesions and systemic infections

11 Purpura fulminans : treatment Cefotaxime 2 gr q h or Ceftriaxone 2 gr q 12 h Allergy Vanco 1 gr q 12 h + Aztreonam 2 gr q 6 h or Moxifloxacin 0,4 gr q 24 h or Levofloxacin 0,5 gr q 12 h

12 Community acquired sepsis - immunocompetent adults Infecting organisms –Enterobacteriacae –Staph aureus –Strept pneumoniae & spp –N. meningitidis –Bacteroides spp Treatment –Cefotaxime or Ceftriaxone –Amoxi clav or cefurox + amino

13 IVDU Infecting organisms –Staph aureus Exclude endocarditis Previous antibiotherapy Treatment Oxacilline 2 gr q 6 h or Vancomycine 1 gr q 12h + Genta 2,5 mg/kg q 12 h

14 Asplenia Overwhelming sepsis Stand by therapy –Amoxi clav –Allergy, travel --> Moxifloxacin, Levofloxacin –Vaccination Antibioprophylaxis

15 Asplenia sepsis Infecting organisms –S. pneumoniae –H. influenzae –N. meningitidis –Capnocytophaga spp Treatment –Ceftriaxone or Cefotaxime

16 Nosocomial *sepsis - immunocompetent adult Infecting organisms –Enterobacteriacae –S. aureus –Strep pneumoniae –Bacteroïdes spp –P. aeruginosa –CNS * readmission - nursing home

17 Nosocomial sepsis Local epidemiology Colonization Previous antibiotherapy IV line Urinary catheter Invasive procedure

18 Treatment Vancomycin ? Cefotaxime or Ceftriaxone or Pip/tazo + amino Ceftazidime or Cefepime or Carbapenem + amino

19 Sepsis neutropenia Infecting organisms –Strepto spp –CNS –S. aureus –Enterobacteriacae –P. aeruginosa Colonization Previous antibiotherapy

20 Neutropenia « Low risk » Amoxi clav 2 gr q 6-8 h + Cipro 750 q 12 h OR Ceftriaxone 2 gr q 12 h + Amikacin mg/kg q 24 h

21 Neutropenia « High risk » Ceftazidime 2 gr q 8 h Cefepime 2 gr q 8 h Pip/tazo 4 gr q 6 h Imipenem 750 mg q 6 h Meropenem 2 gr q 8 h + amino ???

22 Toxic shock syndrome Infecting organisms –Strepto A, B, C, –Staph aureus Treatment –Cefazoline 2 gr q 8 h + Clindamycine 600 mg q 8 h

23 Clinical diagnosis Fever sensitivity 85% Menigism70% Altered mental status60% Kernig Sensitivity 5% Specificity 95% Poser la question = y répondre

24 Case presentation 25-year-old man 2-day history of severe headache, fever, neck stiffness 38,3 °C No rash Normal mental status and neurologic examination Pain on neck flexion but able to flex his neck fully No Kernig and Brudzinski signs

25 Contraindications of lumbar puncture Known or suspected space-occupying lesions with mass effect  LP deferred until CT scan Severe uncorrected coagulopathy (INR > 1.5) Trombocytopenia (platelet count < /mm³) Infection at the puncture site (decubitus ulcer) - Glasgow < 13 - Shock

26 When should a computerized tomography scan precede a lumbar puncture ? Age over 60 years Immunocompromised state History of primary neurologic disease, head trauma, neurosurgery History of seizure within the past week Altered mental status, cilated or poorly reactive pupils, occular palsy and focal neurologic abnormalities Papilledema, bradycardia, irregular respiration History of cancer Suspicion of brain abscess (endocarditis, bacteremia …) Empiric anti infective therapy without delay

27 CSF examination Gram stain - Ziehl - Ink Culture (bacteria, fungi, brucella, nocardia …) Bacterial antigens –if antibiotherapy –Gram or culture negative PCR virus + BK Blood culture 60 % + in acute bacterial meningitis

28 CSF characteristics in selected neurologic conditions

29 Purpura, petechia  N. meningitidis Cellulitis face  S. aureus H. influ VRS, VRI  S. pneumoniae H. influ Parotitis  Mumps Endocarditis  S. aureus Septic arthritis  S. pneumoniae S. aureus Pregnancy  Listeria

30 Acute meningitis treatment IV line - blood cultures AB + dexa 10 mg within 30 min(*) LP if no contraindication Chest x-ray Delta scan if needed (*) S. pneumoniae : 4 h N. meningitidis : 2 h LCR

31 Antibiotherapy Listeria : ampi or CTX S. pneumoniae : peni i 10% cef 3 i 1% H. influ :  vaccination

32 Antibiotherapy dosage Penetration - bactericide - CMI Cefotax 2 gr -(4 gr) q 4h (ratio 25%) Ceftriaxone 2 gr q 12h (ratio %) Ampi 2 gr q 4h (ratio %) Cefepime (ratio 10%) Ceftazidime (ratio %) Cotrimoxazole (ratio %)

33 Antibiotic therapy in meningitis IV from the beginning to the end … Standard therapy –7 days for N. meningitidis – days for S. pneumoniae –(14) - 21 days for L. monocytogenes

34 Meningitis : child > 3 months - adults < 50 yrs Infecting organisms –S. pneumoniae –N. meningitidis –H. influ –L. monocytogenes Treatment –Cefotaxime + ampicilline –Ceftriaxone + ampicilline

35 Meningitis : alcoohol - adults < 50 yrs Cellular immune deficiency - Debilitating illness Infecting organisms –S. pneumoniae –L. monocytogenes –N. meningitidis –Gram negative bacilli Treatment –Cefotaxime + ampicilline –Ceftriaxone + ampicilline

36 Meningitis : HIV /AIDS Infecting organisms –C. neoformans –S. pneumoniae –M. tuberculosis –L. monocytogenes –T. pallidum –N. meningitidis –HIV

37 Meningitis : cerebrospinal fluid shunt Infecting organisms –Coag neg staph –S. aureus –Diphteroids –Enterobacteriaceae Treatment –Vancomycin + cefta

38 Meningitis : after cranial or spinal trauma Infecting organisms –S. pneumoniae –H. influ Treatment –Cefotaxime or Ceftriaxone

39 Meningitis after cranial or spinal trauma (> 4 days) Infecting organisms –Enterobacteriaceae –S. aureus –P. aeruginosa –S. pneumoniae Treatment –Vancomycin + ceftazidime

40 People on the move: demographics year million persons live outside of their country of origin (2,9%) of the world's population Population of concern to UNHCR: 21,6 million Refugees 11,7 million Internally displaced persons: million Rural to urban migration: million/year 1-2 million migrate permanently every year 700 million tourist arrivals/year

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46 01643 Malaria risk pyramid for 1 month of travel without chemoprophylaxis Oceania1:5 Africa1:50 South Asia1:250 Southeast Asia1:2500 South America1:5000 Mexico and Central America 1:10 000

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50 Délai d’apparition de malaria selon espèce Schwartz NEJM 2003; 349, 1510

51 Malaria en Belgique Institut de Santé Publique-Louis Pasteur

52 Who dies from travelers’ malaria ? USA & Canada (n = 21) Total (%) No chemo Dealy seeking care 1 5 Missed by MD Lab misdiagnosis 9 43 Mistreatment11 52 MMWR July 20, 2001 & 1999; 48:SS-1 Kain K et al. CMAJ 2001, 164:

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54 Toute fièvre au retour des tropiques est une malaria jusqu’à preuve du contraire !!

55 Contribution de certaines anomalies biologiques au diagnostic de la malaria Thrombopénie : 60-85% Si de plus GB  N : VPP : 77%VPN : 92% Leucopénie ou GB N : quasi-constante CRP: 100% (mais très peu spécifique) Précoce Très élevé // à parasitémie et à évolution  VPN très bonne (probable) si CRP N  LDH :(très) sensible : % peu spécifique : 60%  haptoglobine :  90% des cas VPN élevée de taux N Intérêt potentiel couplé à CRP

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60 Malaria à P. falciparum Règles: Vu la provenance essentiellement africaine des souches isolées en Belgique Hospitaliser si: -patient non immun -patient immun avec > 2% GR+ et/ou critères de gravité Préférer un traitement à base de quinine (5j ± 2j) si malaria sévère(+ doxycycline)

61  La parasitémie peut augmenter durant les premières 24h de traitement (action sur points limités du cycle qui continue à évoluer "malgré" le traitement)  Résistance R 3 est déterminée à 48h (où diminution de 75% doit être obtenue)  La température peut persister pendant 72-96h sans signification péjorative  Si haute suspicion de malaria, et GE (-) : répéter x sur 48h

62 Traitement de la malaria à P. falciparum sévère Bihydrochlorate de quinine –500 mg IV (dans 250ml glucosé ED) en 4h/ 3x/j pdt 3-7j –10 mg/kg (soit 8mg/kg de quinine base) 3x/j chez enfant N.B.: si origine S. Est Asiatique (ou si malaria sévère ?) dose charge : 20 mg/kg (donc 1 seule fois) ou (dès que possible/début si pas V  /peu critères gravité) Sulfate de quinine: 500 mg per os 3x/j pdt 3-7 jours

63 + Doxycycline 200 mg/j puis 100 mg/j pdt 6 j ou Clindamycine 600 mg 3-4x/jour pdt 3-7 j (par exemple, si grossesse)

64 Malaria treatment P. falciparum (zone A) - P. vivax, P. ovale (*) Day 1 : nivaquine 600 mg mg Day 2 : 300 mg Day 3 : 300 mg (*) Primaquine 15 mg q 24 h x 14 days

65 Malaria treatment P. falciparum Malarone P.O 4 x 3 days (food, milky drink) Quinine sulfate 500 mg q 8 h x 3-7 days + Doxy 100 mg q 12h x 7 days Quinine I.V mg/kg over 4 h in 5% dextrose Quinine I.V. 10 mg/kg over 4 h q 8 h + Doxy 100 mg q 12h or Clinda 10 mg/kg q 8h Qt ! Halofantrine ! Mefloquine 2 weeks

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